From Chaos To Calm: A Life Changed By Ketamine

For six years now, life has been really good for James. He has a great job as the creative director of an advertising firm in New York City. He enjoys spending time with his wife and kids.

And it has all been possible, he says, because for the past six years he has been taking a drug called ketamine.

Before ketamine, James was unable to work or focus his thoughts. His mind was filled with violent images. And his mood could go from ebullient to dark in a matter of minutes.

Ketamine "helped me get my life back," says James, who asked that we not use his last name to protect his career.

Ketamine was developed as a human and animal anesthetic in the 1960s. And almost from the time it reached the market it has also been used as a mind-bending party drug.

But ketamine's story took a surprising turn in 2006, when researchers at the National Institutes of Health showed that an intravenous dose could relieve severe depression in a matter of hours. Since then, doctors have prescribed ketamine "off label" to thousands of depressed patients who don't respond to other drugs.

And pharmaceutical companies are testing several new ketamine-related drugs to treat depression. Johnson & Johnson expects to seek approval for its nasal spray esketamine later this year, though the approval would be limited to use in a clinical setting.

Meanwhile, doctors have begun trying ketamine on patients with a wide range of psychiatric disorders other than depression. And there is now growing evidence it can help people with anxiety, bipolar disorder, post-traumatic stress disorder, and perhaps even obsessive-compulsive disorder.

"I think it's actually one of the biggest advances in psychiatry in a very long time," says Dr. Martin Teicher, an associate professor of psychiatry at Harvard Medical School and director of the Developmental Biopsychiatry Research Program at McLean Hospital.

Ketamine may also offer new hope for people like James who have symptoms of several different psychiatric disorders.

James had a happy childhood, he says. But his thoughts were out of control. "I always felt like I was crossing a freeway and my thoughts were just racing past me," he says.

He spent much of his childhood terrified of "an unknown, an ambiguous force out there." The fear was "overwhelming," he says. "I literally slept with the cover over my head with just room to breathe through my mouth until I went to college."

And there was something else about James: his body temperature.

"I overheated constantly," he says. "I would wear shorts all year long. In my 20s in my apartment I would sleep with the windows open in the middle of the winter."

In his late 20s, James saw a doctor who told him he had attention deficit hyperactivity disorder. So he started taking stimulants.

At first, the pills helped him focus. Then they didn't, no matter how many he took.

He'd done well as an idea guy in the advertising industry. But now James was trying to work at home, and it wasn't going well.

"ADHD pills will make you interested in anything," he says. "So I was putting the desk together and taking the desk apart. I was putting a laptop stand together and taking it apart. I was going in a massive downward spiral."

James had always suffered from mood swings. But now they were rapid and extreme. And he couldn't stop thinking about gruesome scenarios, like a murderer coming for his family.

"My wife took a summer off to be with me because she was scared of what was going to happen to me," he says. "She would go to work for a few hours, then rush home. There would be times I'd call her just screaming, 'Please come home. I can't get through another minute.' "

Eventually, James found his way to Dr. Demitri Papolos, an associate professor of clinical psychiatry at Albert Einstein College of Medicine.

"He was like a whirling dervish when he came into my office," Papolos says. "He was extremely fearful and scanning the environment all the time and he overheated at the drop of a hat."

Papolos diagnosed James with a variant of bipolar disorder he calls the "fear of harm phenotype." It typically appears in childhood and often doesn't respond to traditional psychiatric drugs.

But Papolos has found that the condition does respond to ketamine. "It's been transformational," he says.

In January, Papolos published a study of 45 children with the problem. They inhaled a nasal mist containing ketamine about twice a week. Nearly all got dramatically better.

Scientists still aren't sure why ketamine works, but there's evidence that it encourages the brain to rewire, to alter the connections between cells. That process has been linked to recovery from depression. And it may also explain why ketamine helps people who have symptoms associated with several different psychiatric disorders.

One of those effects involves a part of the brain involved in temperature regulation. And that could explain why patients like James usually stop overheating once they are taking ketamine.

James started taking a ketamine nasal spray every other day. He says his response was dramatic.

"One day I turn to my wife and I'm like, 'I feel calm today. I don't know if it's the sun coming in, I don't know if it's just the way we're sitting here, but I feel like I could go and sit at the computer and work.' "

The next day, James did sit down at his computer. A month later, he was back at work.

Copyright 2018 NPR. To see more, visit http://www.npr.org/.

RACHEL MARTIN, HOST:

One of the country's biggest pharmaceutical companies, Johnson & Johnson, is working on a new drug for depression. It's based on ketamine. Ketamine is a common anesthetic. It's also a popular party drug known as Special K. But doctors are using ketamine to treat an increasingly wide range of psychiatric disorders.

NPR science correspondent Jon Hamilton joins us now in the studio to talk more about this. Hey, Jon.

JON HAMILTON, BYLINE: Hey.

MARTIN: All right. So you have reported a story on this. But first, before we get to that, just tell us a little more about ketamine.

HAMILTON: Well, ketamine is a drug that if you've encountered it, chances are it was in an emergency room. So like, when my kid broke his arm, the drug they used before they set the fracture was ketamine.

MARTIN: Same for my kid. Yeah.

HAMILTON: Yeah. Very effective. And a number of years ago, scientists figured out that ketamine also could be used to relieve depression. This was sort of an accidental discovery. Not only did it relieve depression, but it did it within a matter of hours.

MARTIN: Wow. Within hours?

HAMILTON: Yeah. I mean, it's incredibly fast, especially when you consider that most antidepressants can take weeks to work. And so since then a bunch of psychiatrists have been prescribing it to their patients even though it's not approved for this purpose.

MARTIN: All right. So what does it do, exactly? What's the effect on the body?

HAMILTON: Ketamine is something they call a dissociative. It kind of interrupts the connection between the mind and the body, which is why you don't feel pain anymore. But it also seems to do a lot of different things in the brain, and that is probably why it is likely to be used with a lot of different psychological problems. So I met a guy who had a lot of problems not too long ago. His name is James. He's an advertising executive in New York. And this guy, he's doing great now. He's married with kids, and he feels really good.

JAMES: I've really enjoyed my life in the last, you know, five or six years.

HAMILTON: That's how long he's been taking a small dose of ketamine every other day. Before that, things had become pretty bleak for James, who asked that we not use his full name because doing so might hurt his career. He says even as a child his thoughts were out of control.

JAMES: I always felt like I was crossing a freeway at any given moment and my thoughts were just racing past me, and I would grab one and go with that for a minute.

HAMILTON: James also spent much of his childhood terrified of something he couldn't quite describe.

JAMES: An unknown, an ambiguous force out there. And it was overwhelming. I literally slept with the cover over my head with just room to breathe through my mouth until I went to college.

HAMILTON: And there was something else about James - his body temperature.

JAMES: I overheated constantly. I would wear shorts all year long. In my 20s, in my apartment, I would sleep with the windows open in the middle of the winter.

HAMILTON: In his late 20s, James saw a doctor who told him he had attention deficit hyperactivity disorder. So he started taking stimulants. At first, they helped him focus. Then they didn't no matter how many pills he took. James couldn't work. His mood swings were rapid and extreme, and he was consumed by gruesome thoughts like a murderer coming for his family.

JAMES: My wife took a summer off to be with me 'cause she was scared of what was going to happen to me. She would go to work for a few hours, rush home. There'd be times I'd call her just screaming, please come home; I can't get through another minute.

HAMILTON: Eventually, James found his way to Demitri Papolos, a psychiatrist in Connecticut who treats a lot of patients like James.

DEMITRI PAPOLOS: He was like a whirling dervish when he came into my office. And he was extremely fearful and scanning the environment all the time, and he overheated at the drop of a hat.

HAMILTON: Papolo says people like James have a syndrome that spans several different diagnoses. These include bipolar disorder, attention deficit, sleep disturbances and PTSD. Papolo says conventional psychiatric drugs often don't help much, but ketamine is different.

PAPOLOS: It's been transformational for this syndrome.

HAMILTON: Ketamine is an anesthetic that's often used on children because it's considered so safe. The drug appears to help people with depression by encouraging their brains to rewire quickly. And this rewiring also could be why ketamine helps people like James who have symptoms of several different psychiatric disorders. Martin Teicher, a psychiatrist at McLean Hospital and Harvard Medical School, says ketamine seems to tweak lots of different circuits in the brain.

MARTIN TEICHER: Anti-anxiety, mood stabilization, some degree of antidepressants. So I think it's having, you know, multiple effects and that that means it's probably useful for multiple different disorders.

HAMILTON: Like PTSD, for example.

TEICHER: The animal literature says it is very good in terms of diminishing fear sensitization, which I think is at the core of post-traumatic stress disorder.

HAMILTON: Teicher says ketamine may even prove useful for people with obsessive-compulsive disorder.

TEICHER: I think it's actually one of the biggest advances in psychiatry in a very long time. I mean, it doesn't work for everybody, but it's sort of remarkable to have a treatment that can work pretty much immediately.

HAMILTON: James says he didn't know much about ketamine when he started taking it six years ago.

JAMES: I had heard of it, you know, as a party drug of some sorts.

HAMILTON: And at first, James was on such a small dose that it didn't do much. But as the dose increased, the effect was dramatic.

JAMES: One day, I turned to my wife. I'm like, I feel calm today. I don't know what it is right now. I don't know if it's the sun coming in. I don't know if it's just the way we're sitting here. But I feel like I could go and sit at the computer and work.

HAMILTON: The next day, James did sit down at his computer. A month later, he got a job.

MARTIN: He got a job. So things are better for him now?

HAMILTON: Yeah. He's doing great.

MARTIN: Johnson & Johnson, though, we referenced them in the intro. That company has been working on a prescription drug based on ketamine. How close is it to being approved and marketed?

HAMILTON: Right. This is a drug called Esketamine, and they're working on a form that you take as a nasal spray. And it has finished what they call Phase 3 trials, which is the last step before you submit it to the FDA for approval. They expect to submit it later this year. And it's possible there could be a drug based on this next year sometime.

MARTIN: Are there risks, though?

HAMILTON: There are risks to ketamine. It's a drug of abuse. People become addicted to it sometimes. It can make you hallucinate. And there isn't so much known about what happens when you take it for a long time. People who have abused it for a long time seem to have bladder problems. But beyond that, people really don't know what years of taking ketamine does to you.

MARTIN: And like that doctor said who you spoke with, it works on some people, doesn't work for other people.